Optimizing Outcomes of Treatment-Resistant Depression (TRD) in Older Adults (OPTIMUM): Measures of Psychological Well-Being

Abstract

<h3>Introduction</h3> The "Optimizing Antidepressants for Treatment-Resistant Depression in Older Adults" (OPTIMUM) study, funded by the Patient-Centered Outcomes Research Institute, is a 5-center collaboration that randomized 621 depressed individuals aged 60+ with treatment-resistant depression (TRD), the largest pharmacotherapy trial of TRD in late life. A key goal of this pragmatic trial was to measure outcomes of interest to patients, which in this trial included psychological wellbeing. This construct is closely tied to psychological and physical functioning and can be measured by self-report. <h3>Methods</h3> Participants were recruited and randomized if they were 60 years and older, met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for Major Depressive Disorder, and had a score of 10 or higher on the Patient Health Questionnaire (PHQ-9), despite having been treated with at least two antidepressants with an adequate dosage and for at least four weeks (with previous psychotropic medications being different from the medications being testing in OPTIMUM). Upon study entry, participants were randomized to one of three strategies: augmentation with aripiprazole, augmentation with bupropion, or switch to bupropion. Treatment effectiveness was assessed using the Montgomery Asberg Rating Scale (MADRS) after ten weeks of treatment. Participants were also tested at the beginning and end of this 10-week step with the NIH Toolbox Psychological Well-being battery. Two wellbeing scales were used: positive affect (34 items) and general life satisfaction (16 items). Positive affect is characterized as happiness, contentment, and interest in pleasurable or achievement–relevant activities. Each item is scored on a 5-point scale ranging from "not at all" to "very much". General life satisfaction is the cognitive evaluation of life experiences; items assessing this concept are usually phrased in a general or global way rather than having a momentary or recent recall period. These items administered are scored on either a 5-point or 7-point scale ranging from "strongly disagree" to "strongly agree." <h3>Results</h3> Of the 621 study participants, 212 were randomized to augmentation with aripiprazole, 206 to augmentation with bupropion, and 203 to a switch to bupropion. Participants randomized to augmentation with either aripiprazole or bupropion showed a statistically significant improvement in their general life satisfaction subscale score (aripipirazole: 2.99, p< 0.0001; bupropion: 2.61, p=0.0001), while those switched to bupropion did not. Participants in either of the two augmentation arms also showed a statistically significant improvement in positive affect (aripiprazole: 5.35, p< 0.0001; bupropion: 5.02, p< 0.0001) while those switching to bupropion did not. <h3>Conclusions</h3> Among older adults with TRD, augmentation with aripiprazole or bupropion was associated with a statistically significant improvement in psychological well-being and positive affect, while a switch to bupropion monotherapy did not. Further research is needed to replicate findings. <h3>This research was funded by</h3> Patient-Centered Outcomes Research Institute (PCORI)